HIV and GI Tract Complications: A Comprehensive Clinical Guide [1st ed.] 978-3-030-13376-4;978-3-030-13377-1

Table of contents :
Front Matter ....Pages i-x
Disorders of the Esophagus (Alexander Perelman, Houman Rezaizadeh)....Pages 1-10
HIV and the Stomach (Sidney Olefson, Haleh Vaziri)....Pages 11-24
Biliary Tree and Gallbladder Pathology in HIV (Sarah Banks, Kavita Prabhakar)....Pages 25-35
Disorders of the Liver Excluding Hepatitis A, B, C, D, and E (Nishaal Antony, James H. Lewis, Gayle P. Balba)....Pages 37-90
Viral Hepatitis (Rahul Mahapatra, Jack Fuhrer)....Pages 91-133
Disorders of the Pancreas (Mary Snayd, Ulysses Wu)....Pages 135-148
Disorders of the Small Bowel (Ann Palmer, Henry Anyimadu)....Pages 149-172
Disorders of the Colon and Rectum (Isaiah P. Schuster, Ramona Rajapakse)....Pages 173-192
Back Matter ....Pages 193-199

Citation preview

Clinical Gastroenterology Series Editor: George Y. Wu

Lisa M. Chirch Jurate Ivanaviciene Editors

HIV and GI Tract Complications A Comprehensive Clinical Guide

Clinical Gastroenterology

Series Editor: George Y. Wu Division of Gastroenterology-Hepatology University of Connecticut School of Medicine Farmington, CT, USA

More information about this series at http://www.springer.com/series/7672

Lisa M. Chirch  •  Jurate Ivanaviciene Editors

HIV and GI Tract Complications A Comprehensive Clinical Guide

Editors Lisa M. Chirch Division of Infectious Diseases University of Connecticut School of Medicine Farmington, CT USA

Jurate Ivanaviciene Division of Infectious Diseases St. Vincent’s Medical Center Bridgeport, CT USA

ISSN 2197-7399     ISSN 2197-7704 (electronic) Clinical Gastroenterology ISBN 978-3-030-13376-4    ISBN 978-3-030-13377-1 (eBook) https://doi.org/10.1007/978-3-030-13377-1 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Humana Press imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

The last three decades have witnessed dramatic strides in our ability to successfully treat and manage infection with the human immunodeficiency virus (HIV). The ongoing development and availability of more effective and better-tolerated antiretroviral (ARV) medications have contributed to this, resulting in virologic suppression in a majority of patients taking ARVs. The rollout of certain ARVs for pre-exposure prophylaxis or “PrEP” represents an example of successful innovation to reduce the number of new infections. However, we continue to see new increasing numbers of new infections, particularly in certain patient populations, such as young men who have sex with men (MSM) and those of Hispanic or African descent. Coinfection with other viruses, such as hepatitis C virus (HCV), addressed later in this book, represents a significant ongoing challenge, especially as it relates to the opioid epidemic. End organ damage, such as liver cirrhosis and failure in this case, but also cardiovascular and renal disease, and malignancy, may now present more of an existential threat to individuals living with HIV, even those with well-­ controlled infection. To this end, this book will explore the entire gastrointestinal tract and describe its relationship with HIV, detailing the myriad potential manifestations related to opportunistic infections, medications, and HIV-related malignancy, among others. Chapters are organized by organ system within the GI tract, with liver diseases covered in two separate chapters, one focusing on viral hepatitis. It is our hope that the information summarized in this work will help guide clinicians who care for this patient population in their continued efforts to improve quality and extend survival in those living with HIV infection. Farmington, CT, USA 

Lisa M. Chirch, MD, FIDSA

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Contents

1 Disorders of the Esophagus��������������������������������������������������������������������    1 Alexander Perelman and Houman Rezaizadeh 2 HIV and the Stomach������������������������������������������������������������������������������   11 Sidney Olefson and Haleh Vaziri 3 Biliary Tree and Gallbladder Pathology in HIV ����������������������������������   25 Sarah Banks and Kavita Prabhakar 4 Disorders of the Liver Excluding Hepatitis A, B, C, D, and E������������   37 Nishaal Antony, James H. Lewis, and Gayle P. Balba 5 Viral Hepatitis������������������������������������������������������������������������������������������   91 Rahul Mahapatra and Jack Fuhrer 6 Disorders of the Pancreas������������������������������������������������������������������������  135 Mary Snayd and Ulysses Wu 7 Disorders of the Small Bowel������������������������������������������������������������������  149 Ann Palmer and Henry Anyimadu 8 Disorders of the Colon and Rectum ������������������������������������������������������  173 Isaiah P. Schuster and Ramona Rajapakse Index������������������������������������������������������������������������������������������������������������������  193

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Contributors

Nishaal  Antony, MD  Division of Infectious Diseases, Georgetown University Medical Center, Washington, DC, USA Henry Anyimadu, MD, FACP, FIDSA, AAHIVS  Division of Infectious Diseases, The Hospital of Central Connecticut, New Britain, CT, USA Gayle  P.  Balba, MD  Division of Infectious Diseases, Georgetown University Medical Center, Washington, DC, USA Sarah  Banks, MD  Division of Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT, USA Jack  Fuhrer, MD  Division of Infectious Diseases, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA James H. Lewis, MD, FACP, FACG  Division of Gastroenterology, Georgetown University Medical Center, Washington, DC, USA Rahul Mahapatra, DO  SUNY Upstate Medical University, Syracuse, NY, USA Sidney  Olefson, MD, MBA  Division of Gastroenterology & Hepatology, University of Connecticut School of Medicine, Farmington, CT, USA Ann  Palmer, MD  Division of Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT, USA Alexander  Perelman  Division of Gastroenterology, University of Connecticut School of Medicine, Farmington, CT, USA Kavita Prabhakar, MD  Division of Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT, USA Ramona Rajapakse, MD, FRCP  Division of Gastroenterology and Hepatology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA Houman  Rezaizadeh  Division of Gastroenterology, University of Connecticut School of Medicine, Farmington, CT, USA ix

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Contributors

Isaiah P. Schuster, MD  Division of Gastroenterology and Hepatology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA Mary Snayd  Division of Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT, USA Haleh  Vaziri, MD  Division of Gastroenterology & Hepatology, University of Connecticut School of Medicine, Farmington, CT, USA Ulysses Wu  Division of Infectious Diseases, Saint Francis Hospital and Medical Center, Hartford, CT, USA

Chapter 1

Disorders of the Esophagus Alexander Perelman and Houman Rezaizadeh

Chapter content: In this chapter we will focus on the esophageal manifestations of HIV infection. We will review clinical features of common OIs and noninfectious complications of HIV, as well as diagnostic and therapeutic approaches for clinicians.

Clinical Presentation The clinical presentation of esophageal disease is frequently nonspecific, thus making it difficult to decipher common esophageal disorders such as gastroesophageal reflux and esophageal dysmotility from HIV-associated complications. In patients who are adherent to their ART regimens, viremia is often undetectable, and upper GI symptoms tend to be unrelated to their HIV-positive status [11]. Symptoms most commonly associated with the use of ART relating to the GI tract include nausea, vomiting, diminished appetite, and weight loss. Pancreatitis had previously been reported but is less common with newer regimens. Patients commonly present with complaints of dysphagia, odynophagia, and retrosternal pain. Typically, there is no clear association between symptoms and the underlying pathology. Although a prior study found an association with odynophagia and esophageal ulceration, the underlying cause of the ulcer was difficult to identify [12].

A. Perelman (*) · H. Rezaizadeh Division of Gastroenterology, University of Connecticut School of Medicine, Farmington, CT, USA e-mail: [email protected] © Springer Nature Switzerland AG 2019 L. M. Chirch, J. Ivanaviciene (eds.), HIV and GI Tract Complications, Clinical Gastroenterology, https://doi.org/10.1007/978-3-030-13377-1_1

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Opportunistic Infections Opportunistic infections of the esophagus are most commonly caused by fungi and viruses [11]. Although OIs can occur in patients with normal CD4 counts, as the cell population declines below 200 cells/mm3, OI incidence rates increase.

Esophageal Candidiasis Esophageal candidiasis is the most common OI affecting the esophagus and frequently occurs concomitantly with oral thrush leading to localized infection without candidemia. Local infection predominates as Candida species prefer the keratinized squamous epithelium of the oral mucosa and esophagus [13]. Candida species most commonly seen in association with esophagitis is C. albicans; however, C. glabrata, C. dubliniensis, and C. krusei have also been isolated [14]. Manifestation of disease requires a two-step process, colonization and invasion. Up to 20% of healthy individuals are colonized with Candida species without clinical symptoms [15], with active infection occurring with waning immunity. Clinical presentation includes dysphagia, odynophagia, and retrosternal pain, with or without concomitant oral thrush. (Endoscopy can be beneficial in making the diagnosis, but data support an empiric trial of fluconazole in patients suspected of having esophageal candidiasis [16]. If symptoms fail to resolve after the trial, endoscopic evaluation is warranted.) The characteristic endoscopic findings of esophageal candidiasis are erythematous mucosa covered with plaque-like lesions ranging in color from white to yellow. The plaques are difficult to wash off, however can be brushed or biopsied for laboratory testing. The extent of disease can be described using endoscopic Kodsi criteria (Fig. 1.1) [17]. However, the degree of severity on endoscopy does not appear to correlate to the degree of immunosuppression [11]; thus patients with relatively normal CD4 cell counts may still experience severe candida esophagitis. Failure to respond to fluconazole may be indicative of resistant organisms; in such instance, itraconazole, posaconazole, voriconazole, echinocandins, or intravenous therapy with amphotericin b deoxycholate is recommended. In patients with recurrent candida esophagitis, chronic suppressive treatment is currently recommended with 100–200 mg of fluconazole given three times per week [16] (Table 1.1).

Histoplasmosis Histoplasma capsulatum is a dimorphic fungus present throughout the Midwestern United States and Central and South America [19]. The likelihood of developing

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a

b

c

d

e

f

Fig. 1.1  Esophageal candidiasis Kodsi severity grading (a) Grade I, a few raised white plaques up to 2 mm in size without edema or ulceration. (b) Grade II, multiple raised white plaques greater than 2 mm in size without ulceration. (c) Grade III, confluent, linear, and nodular elevated plaques. (d) Grade IV, finding of grade III with increased friability of the mucous membranes and occasional narrowing of the lumen. (e) “White carpet” appearance, thick white plaque cover on esophageal mucosa circumferential narrowing the lumen. (f) Oral candidiasis, in which endoscopy can detect laryngopharyngeal candidiasis [17]

histoplasmosis and severity of illness directly correlate to the impairment of the immune system, particularly with CD4 cell counts below 200 cells/mm3. Gastrointestinal manifestations are common; however esophageal involvement is reported in only 3% [19, 20]. Dysphagia and odynophagia are the most common presenting symptoms. They can occur secondary to extrinsic compression of the esophagus in the settings of disseminated histoplasmosis resulting in profound lymphadenopathy [18, 20]. Symptoms may also occur from direct infection of the esophageal mucosa causing ulceration. The endoscopic appearance is nonspecific, requiring tissue biopsy to make the diagnosis in isolated cases. Gomori’s methenamine silver stain demonstrates the typical appearance of yeast organisms contained within macrophages, while urinary or serologic testing can be used to support the diagnosis [21, 22]. Therapy for mild to moderate disease consists of itraconazole for a period of at least 12 months. The dose is generally adjusted for interactions with ART agents and a goal serum concentration of greater than 1 μg/mL. Alternative regimens are available if patients are not able to tolerate itraconazole. In cases of severe disseminated disease, liposomal amphotericin B remains the drug of choice [23].

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Mycobacterium Species Mycobacterial infections are OIs typically associated with significant decline in CD4 cell counts. Patients are at risk for infection with Mycobacterium tuberculosis (MTb) and Mycobacterium avium complex (MAC) for which prophylactic antibiotics are initiated once CD4 cell counts fall below 50 cells/mm3. Typically, both manifest as systemic and pulmonary disease with little involvement of the gastrointestinal tract [23]. However, patients suffering from pulmonary MTb infections have been reported to have esophageal symptoms secondary to erosion of mediastinal lymph nodes into the esophagus. In these cases, the mucosa may appear ulcerated or hypertrophic with a granulomatous appearance and possible formation of fistulas [11]. Treatment options are aimed at the underlying systemic infection and HIV with use of ART; if a fistula has developed, it may require endoscopic or surgical intervention.

Herpesviridae Family Viral esophagitis is the most common OI affecting the esophagus after candida esophagitis. The Herpesviridae family of double-stranded DNA viruses are the most common pathogens with cytomegalovirus (CMV) being isolated most frequently, followed by herpes simplex virus (HSV) 1 and 2.

CMV CMV esophagitis is the most common gastrointestinal manifestation second only to colonic infection [24]. Patients typically present with symptoms once CD4 cell counts fall below 100 cells/mm3 and activation of the dormant virus occurs. Symptoms are difficult to distinguish from other causes of esophagitis, typically presenting as dysphagia, odynophagia, and epigastric pain. Patients may appear to be drooling and report a fear of food due to severe odynophagia likely from esophageal ulceration. Endoscopy is helpful in making the diagnosis. Although there are no stereotypical features of CMV esophagitis that have been identified in the literature, some suggest presence of multiple, shallow ulcers greater than 1 cm as being indicative of CMV infection [25]. Confirmation of the diagnosis continues to be a challenge with large numbers of biopsy samples necessary to identify the organism, with the highest yield coming from samples taken from the center of the ulcer. While modern immunohistochemical (IHC) techniques have improved yields, the same cannot be said for esophageal brushings and viral cultures [26, 27]. The histopathologic features of

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CMV esophagitis are similar to those from other anatomic sites, demonstrating giant cells with large nuclei and basophilic inclusions referred to as “owl’s eyes.” CMV esophagitis therapy depends on the severity of disease and the ability of patients to tolerate an oral regimen. For patients with mild disease who are not taking ART, CMV-specific treatment can be delayed, while ART therapy plans are optimized. In individuals with severe disease limiting oral intake, an intravenous regimen with ganciclovir is recommended. Once symptoms improve, patients can be transitioned to an oral valganciclovir [23].

HSV Similar to CMV esophagitis, HSV infections are very common in the general population with resultant dormant infection that reactivates with the decline of cellular immunity. Herpes simplex virus serotype 1 more commonly causes HSV esophagitis compared to serotype 2, with male patients more likely to be affected [28]. At presentations patients may have concomitant herpes labialis and oropharyngeal lesions [29]. The most common symptoms include dysphagia and odynophagia (fever and retrosternal chest pain can be present in 50% of patients). Esophageal findings in HSV disease have a characteristic appearance with well-­ circumscribed ulcers, smaller than 2 cm in size. The ulcer margins have a raised architecture resulting in the classic volcano-like appearance [30]. Unlike in CMV esophagitis, the diagnosis of HSV esophagitis can be made endoscopically and confirmed on histopathology, with highest yield samples coming from the ulcer edges. On hematoxylin and eosin staining, multinucleated giant cells are seen with eosinophilic Cowdry A bodies suggestive of HSV infection. The diagnosis is further supported with IHC staining that is specific for HSV [31]. Treatment of HSV esophagitis is recommended for 2–3 weeks. Oral acyclovir, valacyclovir, and famciclovir are preferred agents for HSV esophagitis treatment. If oral regimen cannot be tolerated due to severity of symptoms, intravenous acyclovir may be used. Patients with confirmed HSV esophagitis who fail to respond to therapy may be infected with an acyclovir-resistant strain, in which case a foscarnet is recommended [23].

HHV-8 Unlike the previously discussed Herpesviridae members, human herpes virus 8 is not associated with esophagitis, but rather a low-grade vascular tumor. It was first described by the Hungarian dermatologist, Moritz Kaposi in 1872. Kaposi’s

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sarcoma (KS) is classified into four variants which are all associated with HHV8 infection. One of these variants, AIDS-related Kaposi’s, is the most common gastrointestinal malignancy in AIDS patients [32]. These submucosal tumors consist of vascular spindle-shaped cells thought to originate from the endothelium [33]. Kaposi’s sarcoma is 20 times more common in AIDS-infected homosexual men than in AIDS-infected heterosexual patients after correcting for degree of immunosuppression. This is thought to be related to higher transmission rates of HHV8 in patients practicing anal and oral sex [32, 34]. It can be directly related to the degree of immunosuppression, however it can also be seen at any point during the course of HIV infection. Cutaneous lesions can be seen frequently in patients with concomitant visceral disease. The esophageal tumors of KS are likely to be asymptomatic but can manifest with mild nausea, vomiting, dysphagia, and catastrophic gastrointestinal bleeding. Endoscopy reveals KS lesions with a distinct purple appearance; however biopsy is of low yield due to the submucosal location resulting in frequent falsenegative results. If adequate samples are obtained, staining for CD34, CD31, and LANA-1 (latency-associated nuclear antigen) helps detect later stages of disease [34]. Treatment of KS depends on the severity of HIV and KS tumor burden. In appropriate cases, ART alone may be considered. Prognosis is poor in most cases with chemotherapy focusing on palliation. Regimens usually consist of liposomal anthracycline with response rates of approximately 45% [32, 35].

Idiopathic Ulcer Similar to CMV and HSV esophagitis, patients with idiopathic esophageal ulcers (IEUs) present with odynophagia, dysphagia, and retrosternal chest pain. It is more commonly seen in patients with CD4 cell counts below 50 cells/mm3 but may occur at any stage of disease. Those with severe symptoms may appear dehydrated and complain of weight loss secondary to food avoidance [11]. During endoscopy, IEUs can be confused for the ulcers of CMV and HSV but generally appear to be larger with deeper penetration into the muscularis propria layer with irregular margins [11, 36]. The diagnosis is alluded to the endoscopic appearance and failure to identify other causative agents on endoscopy and pathology. Some data suggest that HIV itself is the causative agent. A recent study found that in 75% of AIDS patients with IEUs, HIV was found on esophageal biopsy [36]. Treatment is aimed at controlling the viremia with the use of ART, while other authors suggest the use of steroids and proton pump inhibitors to optimize healing [37, 38].

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Table 1.1  Common causes of esophagitis in patients with HIV Candida spp. Etiology [16, 17] Clinical Dysphagia, presentation odynophagia, retrosternal pain, can present with concomitant oral thrush. Typically seen when CD4